The Leech Nervous System: A Valuable Model to Study the Microglia Involvement in Regenerative Processes

Abstract

Microglia are intrinsic components of the central nervous system (CNS). During pathologies in mammals, inflammatory processes implicate the resident microglia and the infiltration of blood cells including macrophages. Functions of microglia appear to be complex as they exhibit both neuroprotective and neurotoxic effects during neuropathological conditions in vivo and in vitro. The medicinal leech Hirudo medicinalis is a well-known model in neurobiology due to its ability to naturally repair its CNS following injury. Considering the low infiltration of blood cells in this process, the leech CNS is studied to specify the activation mechanisms of only resident microglial cells. The microglia recruitment is known to be essential for the usual sprouting of injured axons and does not require any other glial cells. The present review will describe the questions which are addressed to understand the nerve repair. They will discuss the implication of leech factors in the microglial accumulation, the identification of nerve cells producing these molecules, and the study of different microglial subsets. Those questions aim to better understand the mechanisms of microglial cell recruitment and their crosstalk with damaged neurons. The study of this dialog is necessary to elucidate the balance of the inflammation leading to the leech CNS repair.

Gene network underlying the glial regenerative response to central nervous system injury

“…Injury provokes a change in glial cell shape, glia become phagocytic and engulf cell debris and apoptotic cells. This function is accomplished by microglia (which originate from blood cell lineages) in mammals, and by various glial cell types in invertebrates, including also cells from blood lineages (Smith et al, 1987;Mcglade-Mcculloh et al, 1989;Bale et al, 2001;Peruzzi and Sonetti, 2004;Le Marrec-Croq et al, 2013). In fruit flies, a unique mesencephalic astrocyte derived neurotrophic factor (MANF) positive cell type found in pupal brains has been proposed to be microglia-like (Stratoulias and Heino, 2015).…”

Microglia of medicinal leech (Hirudo medicinalis) express a specific activation marker homologous to vertebrate ionized calcium‐binding adapter molecule 1 (Iba1/alias aif‐1)

“…The leech CNS consists of a ventral nerve cord formed by segmental ganglia linked to each other by connective fibers. This structure contains a few, giant glial cells and thousands of resident microglial cells that are spread all along the nerve cord (Coggeshall and Fawcett, ; Jansen and Nicholls, ; Le Marrec‐Croq et al, ). Unlike in Vertebrates, leech CNS does not possess any astrocytes or oligodendrocytes.…”

“…Unlike in Vertebrates, leech CNS does not possess any astrocytes or oligodendrocytes. Nerve repair events involve the action of resident microglia and begin with a rapid activation of microglial cells leading to a morphological modification and to their accumulation at the lesion site (Morgese et al, ; Le Marrec‐Croq et al, ). ATP and NO are involved in microglia migration towards the site of injury (Duan et al, ; Arafah et al, ); the inhibition of these diffusible molecules reduces microglial accumulation, consequently delaying the sprouting of damaged axons (Ngu et al, ).…”

Functional Morphology of the Arm Spine Joint and Adjacent Structures of the Brittlestar Ophiocomina nigra (Echinodermata: Ophiuroidea)

“…Mashanov, unpublished observations) are in intimate contact with the cells of the capsular epithelium. Their topological relationship with the juxtaligamental perikarya and their ultrastructure indicate that the capsular cells are a type of neuroglia: (1) partition-like extensions of the capsular cells separate adjacent juxtaligamental perikarya, which resembles the compartmentalisation of neurons by “packet” glial cells in leech ganglia [94]; (2) the presence in the cells of heterogeneous phagosome-like vacuoles whose contents include cell debris suggests they have a microglia-like scavenger function [95], as has been noted for cells with a similar ultrastructure associated with the peripheral nerves of another ophiuroid [16]. In their description of the spine ligament node of Amphipholis squamata (Delle Chiaje, 1828), Deheyn et al [93] referred to the capsular cells as “type D” cells, which, like those of O .…”